Relapse in the External Auditory Canal of Acute Promyelocytic Leukemia after Treatment with All-Trans Retinoic Acid.

Abstract

A 54-year-old female was admitted to our hospital for gingival bleeding and was diagnosed as acute promyelocytic leukemia (APL). She received induction therapy according to the AML92 protocol of the Japan Adult Leukemia Study Group (JALSG) with all-trans retinoic acid (ATRA) plus chemotherapeutic agents. She achieved complete remission, but one year later had a relapse in her external auditory canal without leukemic cell in the bone marrow. Extramedullary disease is rare in APL.This case suggests the importance of careful observation for extramedullary relapse in patients whoare treated with ATRA.

External Auditory Canal and Middle Ear Relapse of Acute Promyelocytic Leukemia Treated With Arsenic Trioxide

“…Physicians treating these patients should be aware of this ''sanctuary'' site of late relapse having every patient with ear complaints carefully evaluated. 5 We reviewed the literature and, to our knowledge, 4 such cases have been reported in Japanese language [6][7][8][9] and 19 others have been reported in English. 2,10-15 They occurred 2 to 24 months after a variety of induction therapies, including chemotherapy alone, combination therapy with ATRA, and autologous BM transplantation.…”

Treatment of acute promyelocytic leukemia: strategy toward further increase of cure rate

“…Although the CNS relapse was seen only in the APL 92 study, the incidence was not significantly higher than that of previous two studies (P ¼ 0.148). Since relapses at auditory canal are noteworthy and rarely reported previously, 73,75 it is quite possible that ATRA itself may contribute to these extramedullary relapses or that the therapeutic concentration of RA may not reach leukemia cells in these sanctuaries. Careful observation of extramedullary relapses as well as sufficient doses of cytotoxic drugs will be necessary in patients with APL who have been induced into CR by ATRA-based therapy.…”

“…70 A growing body of evidence, however, shows that an extramedullary relapse of APL is frequently observed among patients who have been induced into CR by ATRA regimens, including some hitherto rare relapse sites such as the external auditory canal. [71][72][73][74][75] There are a couple of explanations why extramedullary relapse is more common in patients treated with ATRA. First, ATRA reportedly upgrades the transcription of some leukocyte adhesion molecule genes, and thus ATRA-treated leukemia cells may show increased expression of adhesion molecules.…”

Ear involvement in acute promyelocytic leukemia at relapse: a disease-associated ‘sanctuary’?

“…To the best of our knowledge, a total of seven cases of APL relapse in the ear have been reported to date. [20][21][22][23][24] All these ear relapses were described as case reports and were diagnosed in Japan (five cases) [20][21][22][23] or in Hong Kong (two cases). 24 Three of the five reports were published in Japanese [21][22][23] and two in the English literature.…”

“…18 Amongst EM sites involved in leukemias, infiltration of the ear is exceedingly infrequent and only anecdotal cases have been reported to date. [19][20][21][22][23][24] Anatomical and or biological reasons underlying this particular disease localization are unknown. In the present study, we report seven cases of APL relapse in the auditory apparatus, four of which were observed at a single institution.…”